Medical device with hydrophilic coating

ABSTRACT

A medical device is disclosed, comprising a substrate and a hydrophilic surface coating arranged on said substrate. The substrate has, on its surface coated with said hydrophilic surface coating, a surface texture with an arithmetical mean deviation of the surface profile (Ra) of at least 3 μm and/or a profile section height difference (Rdc (1-99%)) of at least 18 μm. It has surprisingly been found that the increased surface roughness of the substrate provides significant improvements in e.g. water retention for the hydrophilic coating.

This application is a Continuation of copending application Ser. No.12/425,701, filed on Apr. 17, 2009, which claims priority under 35U.S.C. §119(e) on U.S. Provisional Application No. 61/071,217 filed onApr. 17, 2008, and under 35 U.S.C. §119(a) on Patent Patent ApplicationNo. 08154718.4 filed in European Patent Community on Apr. 17, 2008, theentire contents of all of the above applications are hereby incorporatedby reference into the present application.

FIELD OF THE INVENTION

The present invention generally relates to medical devices which presenta substrate, such as an elongate shaft, having an outer hydrophilicsurface coating. In particular the invention relates to a catheter forinsertion into a passageway in a human or animal body, and specificallyurinary catheters. The invention is also related to a correspondingmethod of manufacture and use.

BACKGROUND OF THE INVENTION

Many medical devices incorporate elongate shafts such as tubes which areintended for insertion into and through passageways of a living bodysuch as those of the urethral tract and the cardiovascular system. Themost common type of this general grouping of medical devices are knownas catheters. Exemplary catheters include those designated forurological, angioplasty and valvuloplasty uses, that is, adaptedrespectively for insertion into the urethra, the lumen of a blood vesseland heart passageway of a living body, normally a human body.

Because of the intended use of such medical devices certain parametersneed to be satisfied by the material from which the elongate shaft ismanufactured. The material must fulfill such requirements as softness,good kink resistance, good dimensional stability, processability, forexample ease to form and glue, and the possibility to be sterilized byradiation, steam, ethylene oxide or other means. There is further theneed for the material to accept a surface treatment which will impartdesired surface properties to the medical device, such ashydrophilicity. To this latter end, it is of utmost importance to find asubstrate material that enables the possibility to coat the substrate.

Further, a well-recognized problem with hydrophilic coatings or layershas been that the hydrophilic polymer surface may lose water and dry outwhen it comes in contact with e.g. a mucous membrane, such as when thecatheter is inserted into the urethra. This occurs because of adifference between the osmotic potential of the hydrophilic surface andthe osmotic potential of the mucous membrane. The mucous membrane has ahigher osmotic potential, i.e. a higher salt concentration, than thehydrophilic surface. This difference in osmotic potential causes thewater to go from the hydrophilic surface layer to the mucous membrane sothat the difference in the salt concentration will be counter-balanced.Naturally, this affects the low-friction properties of the hydrophilicouter surface coating, and may lead to pain and injuries of the patient.For this reason, the present applicant has previously developed animproved hydrophilic coating, in which an osmolality-increasing compoundwas applied to a non-reactive hydrophilic polymer surface, therebyproducing a more stable hydrophilic surface, as is disclosed in EP 217771. Hereby, the theretofore prevailing problem of the hydrophiliccoating drying out when inserted into the urethra, thus rendering thearticle insufficiently hydrophilic, was alleviated.

Similar hydrophilic coatings incorporating an osmolality-increasingcompound are discussed in WO 94/16747 disclosing a process in which theosmolality-increasing compound is added during the process of applyingthe hydrophilic coating to the base material, EP 586 324 and EP 591 091disclosing a hydrophilic coating comprising a non-dissolved, solidosmolality-increasing compound e.g. in the form of a powder or grain,and EP 991 702 disclosing a cross-linked hydrophilic coating comprisinga water soluble osmolality-increasing compound.

However, these known methods and coatings are affected by some problems.For example, the production processes, involving different manners ofincorporating the osmolality-increasing compounds in the coatings, arerather tedious cumbersome and costly. Further, the properties of theresulting, wetted hydrophilic surface coating to be inserted into thepatient are, at least to a certain extent, affected by parameters of thewetting process, such as the quantity of wetting fluid used for thewetting, the constituents of the chosen wetting fluid, and the timeperiod during which the wetting is carried through. Since several suchparameters may be unknown beforehand, and may vary to a significantdegree, the properties of the resulting, activated coating becomeunpredictable as well.

Thus, there is a general problem of known medical devices withhydrophilic coatings that water retention in the coating is too low,especially after leaching, or that the coating has too poor adherence tothe substrate, and/or that the means used for prolonging the waterretention time and the adherence of the coating is too costly and/orharmful to the environment.

There is therefore a need for an improved substrate and or coatingmethod for providing medical devices with a hydrophilic surface coating,which is environmentally acceptable and cost effective, and whichensures that the hydrophilic coating can be adequately adhered and isefficient in use.

SUMMARY OF THE INVENTION

It is a general object of the present invention to alleviate theabove-discussed problems. One particular object of the present inventionis to provide a medical device, such as a urinary catheter, with ahydrophilic surface coating, where the water retention capability of thehydrophilic coating is improved. Other general and specific objects ofthe invention will in part be obvious and will in part appearhereinafter.

These objects are achieved with a medical device and a production methodaccording to the appended claims.

According to a first aspect, there is provided a medical devicecomprising a substrate and a hydrophilic surface coating arranged onsaid substrate, wherein the substrate has, on its surface coated withsaid hydrophilic surface coating, a surface texture with an arithmeticalmean deviation of the surface profile (Ra) of at least 3 μm and/orprofile section height difference (Rdc (1-99%)) of at least 18 μm.Preferably, the surface texture fulfills both the Ra and Rdc (1-99%)criteria.

The arithmetical mean deviation of the surface profile (Ra) and theprofile section height difference (Rdc (1-99%)) are, as used in thisapplication, in correspondence with the definitions provided in ISO4287:1997, with the title “Geometrical Product Specifications(GSP)—Surface texture: Profile method—Terms, definitions and surfacetexture parameters. This definition is also generally in line with thesimilar definitions provided in ISO 11562:1996 titled “GeometricalProduct Specifications (GSP)—Surface texture: Profilemethod—Metrological characteristics of fase correct filters” and ISO4288:1996 titled “Geometrical Product Specifications (GSP)—Surfacetexture: Profile method—Rules and procedures for the assessment ofsurface texture”.

The present inventors have surprisingly found that the water retentionof an hydrophilic surface coating is significantly improved when thehydrophilic coating is applied to a substrate with an increased surfacetexture or surface roughness. This may, at least partly, be due to anincreased adherence to the substrate, which in turn may be due toincreased exposure to bonding sites between the coating and thesubstrate. However, the present patent is not to be bound by anyspecific theory of the origin of the remarkable improvement beingdemonstrated by means of the present invention.

The coating applied on substrates in accordance with the presentinvention also adheres stronger to the substrate, thereby reducing therisk of the coating falling off or being significantly deterioratedduring use. This effect is e.g. evident from the fact that similarimprovements in water retention is experienced even after leaching ofthe coated substrate.

It has been noted that at least up to excessive levels, the improvementin water retention increases even further when the surface texture hasan Ra which exceeds 4.0, and preferably exceeds 5.0. Similarly, thesurface texture preferably has an Rdc (1-99%) which exceeds 20, andpreferably exceeds 25. However, as a preferred upper limit, the surfacetexture has an Ra which is less than 20.0, and most preferably less than15.0, and most preferably equal to or less than 10.0. Similarly, thesurface texture preferably has an Rdc (1-99%) which is less than 75, andpreferably less than 60, and most preferably equal to or less than 50.

Even though it is expected that similar positive effects are present inmany types of substrate materials, it has been demonstrated that theeffect is particularly pronounced in substrates made of a plasticmaterial, and in particular when the substrate comprises a materialselected from the group consisting of: polyether block amid, poly vinylchloride (PVC), and polypropene, polyethen polyamide andstyren-ethen/buten-styren co-polymer. Similarly, it has been found bythe present invention that the improvement is particularly noticeablefor hydrophilic coatings comprising polyvinylpyrrolidone.

According to another aspect of the present invention, there is providedmethod of producing a medical device with a hydrophilic surface coating,comprising the steps of:

providing a substrate material having a surface texture with anarithmetical mean deviation of the surface profile (Ra) of at least 3 μmand/or a profile section height difference (Rdc (1-99%)) of at least 18μm;

coating said substrate material with a hydrophilic surface coating.

According to this aspect of the invention, similar advantages asdiscussed above in relation to the first aspect of the invention are athand.

Preferably, both the Ra and Rdc (1-99%) criteria are fulfilled by thesurface texture of the substrate material.

The hydrophilic coating preferably forms a polyurea network, wherebysaid polyurea network forms a covalent bond to said active hydrogengroups in the substrate. Alternatively, the hydrophilic coating may forman ester bond or an epoxy bond to said active hydrogen groups in thesubstrate.

The step of coating the substrate material preferably comprises thesub-steps of: applying sequentially to the surface of the substratefirst a solution comprising between 0.05 to 40% (weight to volume) of anisocyanate compound and thereafter a solution containing between 0.5 and50% (weight to volume) of polyvinylpyrrolidone and curing at an elevatedtemperature.

However, other hydrophilic coatings are also feasible, such as a coatingcomprising hydrophilic polymers cross-linked directly to the substrate.The cross-linking may be effected by means of irradiation, e.g. byelectron beams or UV light.

These and other aspects of the inventive concept will be apparent fromand elicited with reference to the embodiments described hereinafter.

DESCRIPTION OF PREFERRED EMBODIMENTS

In the following detailed description preferred embodiments of theinvention will be described. However, it is to be understood thatfeatures of the different embodiments are exchangeable between theembodiments and may be combined in different ways, unless anything elseis specifically indicated. The hydrophilic catheters may be used formany different purposes, and for insertion into various types ofbody-cavities. However, the following discussion is in particularconcerned with the preferred field of use, urinary catheters, eventhough the invention is not limited to this particular type ofcatheters. However, it is to be appreciated by those skilled in the artthat the inventive concept is not limited to this type of devices, butcould also be used in many other types of medical devices.

A urinary catheter normally comprises a drainage end, often providedwith a flared rearward portion, and an elongate shaft or tube projectingforwardly from the rearward portion. An open-ended internal lumenextends from the rear end of the rearward portion to a drainage aperturein a rounded tip of the elongate tube. The rearward portion may functionas a connector of the catheter, being connectable to other devices, suchas a urine collection bag, a drainage tube or the like.

At least a part of the elongate tube forms an insertable length to beinserted through a body opening of the user, such as the urethra in caseof a urinary catheter. By insertable length is normally, in the contextof a hydrophilic catheter, meant that length of the elongate tube whichis coated with a hydrophilic material, for example PVP, and which isinsertable into the urethra of the patient. Typically, this will be80-140 mm for a female patient and 200-350 mm for a male patient.

The elongate shaft/tube of the catheter is made of a substrate material.The substrates may be made from any polymer material, which arewell-known in the technical field and to which the said hydrophilicpolymers adhere, such as polyurethanes, latex rubbers, other rubbers,polyvinylchloride, other vinyl polymers, polyesters and polyacrylates.However, preferably the substrate is made of a polymer blend comprisinga polyolefin and a composition having molecules with active hydrogengroups, and preferably a composition having molecules with activehydrogen groups. The polyolefin can comprise at least one polymerselected from the group: polyethene, polypropene, and styrene blockcopolymer (SCBS). The composition having molecules with active hydrogengroups can be a polymer having active hydrogen groups bound to thepolymer via nitrogen, such as polyamide or polyurethane.

The hydrophilic coating is arranged on at least part of the substrateforming the catheter shaft. the hydrophilic polymer coating may comprisematerial selected from polyvinyl compounds, polysaccharides,polyurethanes, polyacrylates or copolymers of vinyl compounds andacrylates or anhydrides, especially polyethyleneoxide,polyvinyl-pyrrolidone, heparin, dextran, xanthan gum, polyvinyl alcohol,hydroxy propyl cellulose, methyl cellulose, copolymer ofvinylpyrrolidone and hydroxy ethylmethyl acrylate or copolymer ofpolymethylvinyl ether and maleinic acid anyhydride. The preferredhydrophilic polymer is polyvinylpyrrolidone.

The coating may also comprise an osmolality-increasing compound, as ise.g. taught in EP 0 217 771.

The substrate is further provided with a pronounced surface texture orsurface roughness on its surface to be covered by the hydrophiliccoating. Such a pronounced surface roughness/texture is easilyproducible by adequately controlling the extrusion process duringmanufacture of the substrate shafts. Specifically, in extrusionequipment having various temperature zones, it is often possible toincrease the surface roughness by increasing the temperature in theearly stages of the extrusion process, and by lowering the temperatureat the later stages, or by making an overall lowering of thetemperatures. However, the temperature settings required for obtainingan adequate surface texture differs between different materials, andalso varies significantly between different extrusion equipment, aswould be known by any one of ordinary skill in the art. Alternatively oradditionally, it is also possible to obtain an adequate surface textureby a surface treatment after extrusion, such as by mechanical rougheningof the surface, chemical etching, plasma surface treatment, e.g. plasmadeposition, electron-beam technology, ion beam sputter texturing,etching, e.g. ion etching, microwave radiation, sputtering, sintering,grinding, polishing, milling, photolithography, laser treatment,microblasting etc.

The surface texture is produced to have at least one, and preferablyboth, of a surface profile (Ra) equal to or exceeding 3 μm and a profilesection height difference (Rdc (1-99%)) equal to or exceeding 18 μm.Preferably, Ra exceeds 4.0, and preferably exceeds 5.0.

Similarly, the surface texture preferably has an Rdc (1-99%) whichexceeds 20, and preferably exceeds 25. However, as a preferred upperlimit, the surface texture has an Ra which is less than 20.0, and mostpreferably less than 15.0, and most preferably equal to or less than10.0. Similarly, the surface texture preferably has an Rdc (1-99%) whichis less than 75, and preferably less than 60, and most preferably equalto or less than 50.

The present inventors have surprisingly found that the water retentionof an hydrophilic surface coating is significantly improved when thehydrophilic coating is applied to a substrate with such an increasedsurface texture or surface roughness.

Some preferred examples of methods for applying a hydrophilic surfacecoating to the substrate will now be discussed in greater detail.However, it is to be noted that the above-discussed substrate materialhaving an increased surface roughness can also be used for many othercoating methods for obtaining an improved hydrophilic surface coating.

A preferred method for coating of the substrate will now be disclosed inmore detail. The outer surface of the elongate shaft is preferablycoated with a stable hydrophilic coating by applying sequentially to thesurface of the substrate first a solution comprising between 0.05 to 40%(weight to volume) of an isocyanate compound and thereafter a solutioncontaining between 0.5 and 50% (weight to volume) ofpolyvinylpyrrolidone and curing at an elevated temperature. Theisocyanate solution may advantageously contain between 0.5 to 10%(weight to volume) of the isocyanate compound, and may preferablycontain between 1 to 6% (weight to volume) of the isocyanate compound.Generally, the isocyanate solution only needs to be in contact with thesurface briefly, for example 5 to 60 sec.

Application of the isocyanate solution to the substrate surface resultsin a coating having unreacted isocyanate groups being formed on thesubstrate surface. Application of the polyvinylpyrrolidone solution tothe substrate surface then results in a hydrophilicpolyvinylpyrrolidone-polyurea interpolymer coating being formed. Curingof this hydrophilic coating binds the isocyanate compounds together toform a stable non-reactive network that binds the hydrophilicpolyvinylpyrrolidone. To advantage, curing takes place in the presenceof a water-containing gas, for example ambient air, to enable theisocyanate groups to react with the water to yield an amine whichrapidly reacts with other isocyanate groups to form a urea cross-link.Further, the method may comprise the steps of evaporating the solvent ofthe isocyanate solution prior to application of the polyvinylpyrrolidonesolution and evaporating the solvent of the polyvinylpyrrolidonesolution prior to curing of the hydrophilic coating. This may forexample be done by air drying.

The isocyanate compound preferably comprises at least two unreactedisocyanate groups per molecule. The isocyanate may be selected from2,4-toluene diisocyanate and 4,4′-diphenylmethane diisocyanate, or apentamer of hexamethylene diisocyanate and toluene diisocyanate ofcyanurate type, or trimerized hexamethylene diisocyanate biuret ormixtures thereof.

The solvent for the isocyanate compound is preferably one which does notreact with isocyanate groups. The preferred solvent is methylenechloride but it is also possible to use ethyl acetate, acetone,chloroform, methyl ethyl ketone and ethylene dichloride, for example.

In order to shorten the necessary reaction times and curing timessuitable catalysts for isocyanate curing may be added. These catalystsmay be dissolved in either the isocyanate solution or thepolyvinylpyrrolidone solution but are preferably dissolved in thelatter. Different types of amines are especially useful, for examplediamines, but also for example triethylenediamine. Preferably, analiphatic amine is employed which is volatisable at the drying andcuring temperatures used for the coating, and which furthermore isnon-toxic. Examples of suitable amines are N,N′ diethylethylendiamine,hexamethylendiamine, ethylendiamine, paradiaminobenzene,1,3-propandiol-para-aminobenzoic acid diester and diaminobicyclo-octane.

The polyvinylpyrrolidone used preferably has a mean molecular weight ofbetween 10⁴ to 10⁷ with the most preferred mean molecular weight beingabout 10⁵. Polyvinylpyrrolidone having such a molecular weight iscommercially available, for example under the trademark Kollidon(R)(BASF). Examples of suitable solvents for polyvinylpyrrolidone that maybe used are methylene chloride (preferred), ethyl acetate, acetone,chloroform, methyl ethyl ketone and ethylene dichloride. The proportionof polyvinylpyrrolidone in the solution is preferably between 0.5 to 10%(weight to volume) and most preferred between 2 to 8% (weight tovolume). The polyvinylpyrrolidone in the solvent is applied by dipping,spraying or the like for a short period of time, e.g. during 5 to 50sec. Curing of the coating is preferably performed at a temperature of50 to 130 deg. C., in for example an oven, for a duration of between 5to 300 min.

In a preferred embodiment the hydrophilic coating contains anosmolality-increasing compound, for instance an inorganic salt selectedfrom sodium and potassium chlorides, iodides, citrates and benzoates.The osmolality-increasing compound may be applied in the manner detailedin EP 0 217 771 by the same applicant.

Experiments

In experimental tests, substrates made of the following substratematerials were used:

-   -   Ex A: Polyether block amid (Pebax)    -   Ex A′: Polyether block amid (Pebax)    -   Ex B: Poly vinyl chloride (PVC)    -   Ex B′: Poly vinyl chloride (PVC)    -   Ex C: A combination of the materials Polypropene, Polyethen        Polyamide and Styren-ethen/buten-styren co-polymer, sold under        the trade name Meliflex    -   Ex C′: Meliflex

The materials of Ex A and Ex A′ are identical, and the only differencebetween the substrates is that Ex A is extruded in such a way that ithas an increased surface roughness compared to Ex A′. Correspondingly,the materials of Ex B and B′ and Ex C and C′, respectively, are alsoidentical, the only difference residing in the surface roughness.

The substrates were coated with identical hydrophilic coating, inaccordance with the method discussed above. Consequently, the catheterswere prepared by dipping the substrates in a primer solution comprisinga diisocyanate (named Desmodur IL), which is dissolved in methylenechloride to a concentration of 2% (weight/volume), for 15 seconds. Thecatheters were thereafter dried at ambient temperature for 60 seconds,and are then dipped for 3 seconds in a solution containing 6%(weight/volume) of polyvinylpyrrolidone (PVP K90) dissolved in methylenechloride. The catheters were then allowed to flush off at 35 deg. C. for30 minutes, and then cured for 60 minutes at 80 deg. C., and werefinally allowed to cool to room temperature and rinsed in water.

Further, an osmolality increasing compound, here NaCl, was subsequentlyadded in accordance with the process described in EP 0 217 771.

For all the substrates, two measures of the surface roughness weremeasured:

-   -   The surface profile Ra [μm], providing a measure of the average        height in pm over the base surface.    -   The profile section height difference Rdc (1-99%) [μm] providing        a measure of the vertical distance between two section lines,        said section lines being arranged at heights being covered by        1.0% and 99.0% of material, respectively.

Ra and Rdc were measured by means of a Hommel Tester T1000 Waveprofilometer. The water retention of the catheters, each pair differingonly in the surface roughness of the substrates being used, were thentested for water retention in ambient air. To this end, the catheterswere wetted during 30 sec., and the water content (mg/cm²) in thehydrophilic coating was determined after 6 minutes. The water contentwas determined by weighing the catheters before wetting, to obtain areference weight, and to measure the catheters a certain time afterwetting, and subtracting the reference weight from this measurement. Theobtained weight difference is a measure on the water content being heldby the hydrophilic coating at the time of measurement.

The results of the surface texture measurements and the water retentionmeasurements are presented in Table 1 below.

TABLE 1 Surface roughness of substrates and water retention [mg/cm²] incoating Water retention after 6 minutes Example Material [mg/cm2] Ra[μm] Rdc [μm] Ex A Pebax 8.97 (+/−0.39) 5.80 (+/−0.70) 33.14 (+/−3.69)Ex A′ Pebax 7.59 (+/−0.24) 0.15 (+/−0.03)  0.88 (+/−0.20) Ex B PVC 5.14(+/−0.39) 7.14 (+/−0.82) 41.99 (+/−4.36) Ex B′ PVC 3.85 (+/−0.32) 0.85(+/−0.31)  5.19 (+/−1.81) Ex C Meliflex 5.50 (+/−0.22) 3.27 (+/−0.32)18.88 (+/−2.03) Ex C′ Meliflex 4.62 (+/−0.21) 1.04 (+/−0.18)  5.79(+/−1.13)

The above-discussed measurement data is mean values of a number ofmeasurement, and the standard deviation is added within parentheses.Thus, the differences discussed in the following are statisticallyreliable, i.e. the standard deviation is significantly smaller than thededuced difference.

From this table it is clearly deducible that Ex A has a significantlyimproved water retention over Ex A′ (Ex A: 8.97 mg/cm2 and Ex A′: 7.59mg/cm2), Ex B has a significantly improved water retention over Ex B′(Ex B: 5.14 mg/cm2 and Ex B′: 3.85 mg/cm2), and Ex C has a significantlyimproved water retention over Ex C′ (Ex C: 5.50 mg/cm2 and Ex C′: 4.62mg/cm2). These improvements is correlated with a significantly increasedsurface texture roughness, and thus with significantly higher values onRa and Rdc, in Ex A compared to Ex A′, in Ex B compared to Ex B′ and inEx C compared to Ex C′.

Based on the above-discussed experiments it is therefore fair toconclude that when using a substrate surface with increased roughness,in these examples with an Ra in the range 3-8 μm and an Rdc (1-99%) inthe range 18-42, the water retention of the coating was significantlyimproved over identical substrates but with a smoother substratesurface, in these examples with an Ra in the range 0.5-1.5 μm and an Rdc(1-99%) in the range 0.5-6.

Similar improvements in water retention were also experienced incatheters subject to leaching for a certain time, such as for 6 minutes.This indicates that the coating on substrate surfaces with increasedroughness also improves the adherence of the coating to the substrates.

In a further line of experiments, similar tests were made on hydrophiliccatheters with a another type of hydrophilic coating. This hydrophiliccoating was cross-linked to the substrate by means of UV-radiation.

As in the above-discussed examples, the materials of these Ex D and ExD′ are identical, and the only difference between the substrates is thatEx D is extruded in such a way that it has an increased surfaceroughness compared to Ex D′. Further, the substrate material used in ExD and D′ are poly vinyl chloride (PVC), similar to the material of Ex Band B′ discussed in the foregoing.

More specifically, catheters having a cross-linked hydrophilic PVPcoating were prepared in by dipping PVC catheter substrates in a primersolution comprising 4.9 parts of Plasdone K 90 (PVP K 90) and 0.1 partsof the photo initiator ESACURE KIP 150 dissolved in 95 parts of anethanol/gamma butyrolactone (85/15) solvent mixture. The catheters weredipped in the primer solution with a speed of 20 mm/s, providing anaverage dipping time of about 20 sec. Subsequently, the catheters weredried for 1 minute at room temperature (20 deg. C.).

Thereafter, the catheters were dipped in a solution of 4 parts ofPlasdone K90 (PVP K 90) dissolved in 96 parts of an ethanol/gammabutyrolactone (85/15) solvent mixture with a speed of 20 mm/s, providingan average dipping time of about 20 sec. The catheters were then driedfor 30 minutes at 70 deg. C. After drying for 30 minutes, thePVC-catheters were exposed to UV-light for 150 sec. The UV source usedemits light at a wavelength of 254 nm

These catheters of Ex D and D′ were, as in the previously discussedexamples, tested in respect of surface profile Ra and profile sectionheight difference Rdc (1-99%) [μm] by means of a Hommel Tester T1000Wave profilometer. Further, the water retention of the catheters weretested for water retention in ambient air, in the same way as discussedabove. The results of the surface texture measurements and the waterretention measurements are presented in Table 2 below.

TABLE 2 Surface roughness of substrates and water retention [mg/cm²] incoating Water retention after 6 minutes Example Material [mg/cm2] Ra[μm] Rdc [μm] Ex D PVC 13.07 (+/−0.18) 7.79 (+/−1.76) 45.88 (+/−9.97) ExD′ PVC 12.62 (+/−0.26) 0.18 (+/−0.03)  1.11 (+/−0.29)

The above-discussed measurement data is mean values of a number ofmeasurement, and the standard deviation is added within parentheses.Thus, the differences discussed in the following are statisticallyreliable, i.e. the standard deviation is significantly smaller than thededuced difference.

From this table it is clearly deducible that Ex D has a significantlyimproved water retention over Ex D′ (Ex D: 13.07 mg/cm2 and Ex D′: 12.62mg/cm2). This improvement is correlated with a significantly increasedsurface texture roughness, and thus with significantly higher values onRa and Rdc (1-99%), in Ex D compared to Ex D′.

Based on the above-discussed experiments it is therefore fair toconclude that this improvement, as discussed above in relation to Tables1 and 2, is not dependent on any particular substrate material, and alsonot dependent on any particular type of hydrophilic coating. On thecontrary, the above-discussed experiments show that the improvement isclearly obtainable in several different substrate materials, and fordifferent types of hydrophilic coatings.

CONCLUSION AND SUMMARY

The invention has now been discussed in relation to differentembodiments. However, it should be appreciated by those versed in theart that several further alternatives are possible. For example, thefeatures of the different embodiments discussed above may naturally becombined in many other ways.

It is further possible to use the invention for other types of cathetersthan urinary catheters, such as vascular catheters or the like. It isalso possible to use many different types of hydrophilic coatings. Manydifferent materials could also be used for the different parts of thecatheter assembly.

It will be appreciated by those versed in the art that several suchalternatives similar to those described above could be used withoutdeparting from the spirit of the invention, and all such modificationsshould be regarded as a part of the present invention, as defined in theappended claims.

1. A urinary catheter comprising a substrate having a surface and ahydrophilic surface coating arranged on said surface of the substrate,wherein the substrate is made of a plastic material and the surface ofthe substrate has, underlying said hydrophilic surface coating, has asurface texture with at least one of the following: an arithmetical meandeviation of the surface profile (Ra) according to ISO 4287:1997 of atleast 3 μm; and a profile section height difference (Rdc (1-99%))according to ISO 4287:1997 of at least 18 μm.
 2. The urinary catheter ofclaim 1, wherein said surface texture has an arithmetical mean deviationof the surface profile (Ra) according to ISO 4287:1997 of at least 3 μmand a profile section height difference (Rdc (1-99%)) according to ISO4287:1997 of at least 18 μm.
 3. The urinary catheter of claim 1, whereinsaid surface texture has an Ra according to ISO 4287:1997 of at least4.0 μm.
 4. The urinary catheter of claim 1, wherein said surface texturehas an Ra according to ISO 4287:1997 less than 20.0 μm.
 5. The urinarycatheter of claim 1, wherein said surface texture has an Rdc (1-99%)according to ISO 4287:1997 of at least 20 μm.
 6. The urinary catheter ofclaim 1, wherein said surface texture has an Rdc (1-99%) according toISO 4287:1997 less than 75 μm.
 7. The urinary catheter of claim 1,wherein the substrate comprises a material selected from the groupconsisting of polyether block amid, poly vinyl chloride (PVC), andpolypropene, polyethen polyamide and styren-ethen/buten-styrenco-polymer.
 8. The urinary catheter of claim 1, wherein the hydrophiliccoating comprises polyvinylpyrrolidone.
 9. A method of producing aurinary catheter with a hydrophilic surface coating, comprising thesteps of: providing a substrate of a plastic material having a surfacetexture with at least one of the following: an arithmetical meandeviation of the surface profile (Ra) according to ISO 4287:1997 of atleast 3 μm; and a profile section height difference (Rdc (1-99%))according to ISO 4287:1997 of at least 18 μm; and coating said substratematerial with a hydrophilic surface coating.
 10. The method of claim 9,wherein the hydrophilic coating forms a polyurea network, whereby saidpolyurea network forms a covalent bond to said active hydrogen groups inthe substrate.
 11. The method of claim 9, wherein the hydrophiliccoating is cross-linked to said substrate by means of irradiation. 12.The method of claim 9, wherein the hydrophilic coating forms an esterbond or an epoxy bond to said active hydrogen groups in the substrate.13. The method of claim 9, wherein the step of coating the substratematerial comprises the sub-steps of: applying sequentially to thesurface of the substrate first a solution comprising between 0.05 to 40%(weight to volume) of an isocyanate compound and thereafter a solutioncontaining between 0.5 and 50% (weight to volume) ofpolyvinylpyrrolidone and curing at an elevated temperature.
 14. Theurinary catheter of claim 1, wherein the substrate comprises: a materialselected from the group consisting of: poly vinyl chloride (PVC);polyether block amid; a combination of polypropene, polyethen, polyamideand styrene-ethen/buten-styren co-polymer; polyesters; polyacrylates;and a polymer blend comprising polyolefin, and a composition havingmolecules with active hydrogen groups, such as polyamide orpolyurethane.
 15. The urinary catheter of claim 14, wherein thepolyolefin comprises at least one polymer selected from the group ofpolyethene, polypropene and styrene block copolymer (SCBS).
 16. Theurinary catheter of claim 1, wherein the catheter has an elongate tubeforming an insertable length to be inserted through a body opening ofthe user, said elongate tube forming said substrate, and wherein theentire insertable length is coated with said hydrophilic surfacecoating.
 17. The urinary catheter of claim 1, wherein said surfacetexture has an Ra according to ISO 4287:1997 in the range of 3.0-15.0μm.
 18. The urinary catheter of claim 1, wherein said surface texturehas an Ra according to ISO 4287:1997 in the range of 3.0-10.0 μm. 19.The urinary catheter of claim 1, wherein said surface texture has an Rdc(1-99%) according to ISO 4287:1997 in the range 18-50 μm.
 20. Theurinary catheter of claim 1, wherein substrate is an extruded tube. 21.The method of claim 9, wherein the step of providing a substrate of aplastic material with the defined surface texture is made by extrusion,whereby the surface texture is obtained by controlling the extrusionprocess.
 22. The method of claim 9, wherein the step of providing asubstrate of a plastic material with the defined surface texturecomprises the sub-step of obtaining the defined surface texture by atleast one of: mechanical roughening of the surface, sintering, grinding,polishing, milling, laser treatment and microblasting.
 23. A method ofproducing a urinary catheter with a hydrophilic surface coating,comprising the steps of: extruding a substrate of a plastic material insuch a way that it obtains a surface texture with at least one of thefollowing: an arithmetical mean deviation of the surface profile (Ra)according to ISO 4287:1997 of at least 3 μm; and a profile sectionheight difference (Rdc (1-99%)) according to ISO 4287:1997 of at least18 μm; and coating said substrate material with a hydrophilic surfacecoating.